Abstract
Purpose: To investigate the anti-depressant activity of kaempferol, quercetin, kaempferol-3-O-β-Dglucose and quercetin-3-O-β-D-glucose isolated from Apocynum venetum Linn. (Apocynaceae) leaf and their mechanisms of action. Methods: The four flavonoids were isolated from Apocynum venetum leaf by chromatography. Mice were divided into vehicle, fluoxetine, kaempferol, quercetin, kaempferol-3-O-β-D-glucose and quercetin- 3-O-β-D-glucose groups (n = 10). Forced swimming (FST), tail suspension (TST) and locomotor activity (LAT) tests were used to evaluate the effects of the four flavonoids (0.35 mM/kg) on immobility time, monoamine neurotransmitters, viz, norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5- HT), as well as on the metabolite (5-HIAA) in mice brain and central nervous system (CNS) with the aid of video camera, HPLC-ECD and activity-monitoring system. Results: The four flavonoids significantly (p < 0.05) reduced mice immobility time (72.58 - 90.24; 52.58 - 70.24 s), 5-HIAA levels (940.8 - 1244.7; 880.8 - 1164.1 ng/g) and 5-HIAA/5-HT ratio (1.77 - 4.76; 1.83 - 4.16), but increased NE, DA and 5-HT levels (238.7 - 405.7, 308.4 - 528.1, 261.4 - 531.9; 243.9 - 423.6, 296.7 - 534.9, 279.8 - 481.4 ng/g) in FST and TST, compared with control group (146.18, 126.18 s; 1363.4, 1240.9 ng/g; 7.43, 6.16; 138.4, 235.4, 183.4 and 143.7, 218.6, 201.4 ng/g). The effects of the four flavonoids on the above indices were significant (p < 0.05) and positively related to their polarity. They had no CNS-stimulating effects in LAT. Conclusion: The anti-depressant activities of the four flavonoids are positively related to their polarity, and the mechanisms may be due to increased NE, DA and 5-HT and reduced 5-HT metabolism. Keywords: Kaempferol, Quercetin, Forced swimming test, Tail suspension test, Locomotor activity test, Neurotransmitters
Highlights
Depression is a kind of mental disorders and its major symptoms include the reduced interest and pleasure, lowered mood and metabolic disorder of monoamine neurotransmitters in the central nervous system (CNS) [1]
The results suggested that the effects of drug treatments on the reductions of immobility time in Forced swimming test (FST) and TST were not induced by possible CNS-stimulating effects
The differences of antidepressant activities of quercetin, quercetin-3-Oβ-D-glucose, kaempferol, kaempferol-3-O-β-Dglucose from A. venetum leaf and the possible mechanisms were investigated by FST, TST and locomotor activity (LAT)
Summary
Depression is a kind of mental disorders and its major symptoms include the reduced interest and pleasure, lowered mood and metabolic disorder of monoamine neurotransmitters in the central nervous system (CNS) [1]. Organization (WHO) predicted that depression will be the second most common disease in 2020 [2]. It’s reported that A. venetum leaf has lots of pharmacological effects such as anti-oxidant [4,5], anti-hypertensive [6], anti-depressant [7]. A series of studies [9,10,11,12,13,14] suggested that the active constituents of anti-depressant activity of A. venetum leaf are total flavonoids. The flavonoids of A. venetum leaf include tamarixetin, kaempferol, quercetin, hyperoside, trifolin, quercetin-3-O-(6"-O-
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